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BACKGROUND: The thalamus has a central role in the pathophysiology of idiopathic cervical dystonia (iCD); however, the nature of alterations occurring within this structure remain largely elusive. Using a structural magnetic resonance imaging (MRI) approach, we examined whether abnormalities differ across thalamic subregions/nuclei in patients with iCD. METHODS: Structural MRI data were collected from 37 patients with iCD and 37 healthy controls (HCs). Automatic parcellation of 25 thalamic nuclei in each hemisphere was performed based on the FreeSurfer program. Differences in thalamic nuclei volumes between groups and their relationships with clinical information were analysed in patients with iCD. RESULTS: Compared to HCs, a significant reduction in thalamic nuclei volume primarily in central medial, centromedian, lateral geniculate, medial geniculate, medial ventral, paracentral, parafascicular, paratenial, and ventromedial nuclei was found in patients with iCD (P < 0.05, false discovery rate corrected). However, no statistically significant correlations were observed between altered thalamic nuclei volumes and clinical characteristics in iCD group. CONCLUSION: This study highlights the neurobiological mechanisms of iCD related to thalamic volume changes.
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Imagen por Resonancia Magnética , Tálamo , Tortícolis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Tortícolis/diagnóstico por imagen , Tortícolis/patología , Imagen por Resonancia Magnética/métodos , Tálamo/diagnóstico por imagen , Tálamo/patología , Adulto , Anciano , Núcleos Talámicos/diagnóstico por imagen , Núcleos Talámicos/patologíaRESUMEN
BACKGROUND AND HYPOTHESIS: Abnormal thalamic nuclei volumes and their link to cognitive impairments have been observed in schizophrenia. However, whether and how this finding extends to the schizophrenia spectrum is unknown. We hypothesized a distinct pattern of aberrant thalamic nuclei volume across the spectrum and examined its potential associations with cognitive symptoms. STUDY DESIGN: We performed a FreeSurfer-based volumetry of T1-weighted brain MRIs from 137 healthy controls, 66 at-risk mental state (ARMS) subjects, 89 first-episode psychosis (FEP) individuals, and 126 patients with schizophrenia to estimate thalamic nuclei volumes of six nuclei groups (anterior, lateral, ventral, intralaminar, medial, and pulvinar). We used linear regression models, controlling for sex, age, and estimated total intracranial volume, both to compare thalamic nuclei volumes across groups and to investigate their associations with positive, negative, and cognitive symptoms. STUDY RESULTS: We observed significant volume alterations in medial and lateral thalamic nuclei. Medial nuclei displayed consistently reduced volumes across the spectrum compared to controls, while lower lateral nuclei volumes were only observed in schizophrenia. Whereas positive and negative symptoms were not associated with reduced nuclei volumes across all groups, higher cognitive scores were linked to lower volumes of medial nuclei in ARMS. In FEP, cognition was not linked to nuclei volumes. In schizophrenia, lower cognitive performance was associated with lower medial volumes. CONCLUSIONS: Results demonstrate distinct thalamic nuclei volume reductions across the schizophrenia spectrum, with lower medial nuclei volumes linked to cognitive deficits in ARMS and schizophrenia. Data suggest a distinctive trajectory of thalamic nuclei abnormalities along the course of schizophrenia.
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Disfunción Cognitiva , Imagen por Resonancia Magnética , Trastornos Psicóticos , Esquizofrenia , Núcleos Talámicos , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/patología , Femenino , Masculino , Adulto , Trastornos Psicóticos/diagnóstico por imagen , Trastornos Psicóticos/patología , Trastornos Psicóticos/fisiopatología , Núcleos Talámicos/diagnóstico por imagen , Núcleos Talámicos/patología , Adulto Joven , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , AdolescenteRESUMEN
BACKGROUND: Previous studies have shown that thalamic and hippocampal neurodegeneration is associated with clinical decline in Multiple Sclerosis (MS). However, contributions of the specific thalamic nuclei and hippocampal subfields require further examination. OBJECTIVE: Using 7 Tesla (7T) magnetic resonance imaging (MRI), we investigated the cross-sectional associations between functionally grouped thalamic nuclei and hippocampal subfields volumes and T1 relaxation times (T1-RT) and subsequent clinical outcomes in MS. METHODS: High-resolution T1-weighted and T2-weighted images were acquired at 7T (n=31), preprocessed, and segmented using the Thalamus Optimized Multi Atlas Segmentation (THOMAS, for thalamic nuclei) and the Automatic Segmentation of Hippocampal Subfields (ASHS, for hippocampal subfields) packages. We calculated Pearson correlations between hippocampal subfields and thalamic nuclei volumes and T1-RT and subsequent multi-modal rater-determined and patient-reported clinical outcomes (â¼2.5 years after imaging acquisition), correcting for confounders and multiple tests. RESULTS: Smaller volume bilaterally in the anterior thalamus region correlated with worse performance in gait function, as measured by the Patient Determined Disease Steps (PDDS). Additionally, larger volume in most functional groups of thalamic nuclei correlated with better visual information processing and cognitive function, as measured by the Symbol Digit Modalities Test (SDMT). In bilateral medial and left posterior thalamic regions, there was an inverse association between volumes and T1-RT, potentially indicating higher tissue degeneration in these regions. We also observed marginal associations between the right hippocampal subfields (both volumes and T1-RT) and subsequent clinical outcomes, though they did not survive correction for multiple testing. CONCLUSION: Ultrahigh field MRI identified markers of structural damage in the thalamic nuclei associated with subsequently worse clinical outcomes in individuals with MS. Longitudinal studies will enable better understanding of the role of microstructural integrity in these brain regions in influencing MS outcomes.
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Hipocampo , Imagen por Resonancia Magnética , Esclerosis Múltiple , Núcleos Talámicos , Humanos , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Masculino , Femenino , Adulto , Núcleos Talámicos/diagnóstico por imagen , Núcleos Talámicos/patología , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Persona de Mediana Edad , Estudios TransversalesRESUMEN
Thalamic abnormalities have been repeatedly implicated in the pathophysiology of schizophrenia and other neurodevelopmental disorders. Uncovering the etiology of thalamic abnormalities and how they may contribute to illness phenotypes faces at least two obstacles. First, the typical developmental trajectories of thalamic nuclei and their association with cognition across the lifespan are largely unknown. Second, modest effect sizes indicate marked individual differences and pose a significant challenge to personalized medicine. To address these knowledge gaps, we characterized the development of thalamic nuclei volumes using normative models generated from the Human Connectome Project Lifespan datasets (5-100+ years), then applied them to an independent clinical cohort to determine the frequency of thalamic volume deviations in people with schizophrenia (17-61 years). Normative models revealed diverse non-linear age effects across the lifespan. Association nuclei exhibited negative age effects during youth but stabilized in adulthood until turning negative again with older age. Sensorimotor nuclei volumes remained relatively stable through youth and adulthood until also turning negative with older age. Up to 18% of individuals with schizophrenia exhibited abnormally small (i.e., below the 5th centile) mediodorsal and pulvinar volumes, and the degree of deviation, but not raw volumes, correlated with the severity of cognitive impairment. While case-control differences are robust, only a minority of patients demonstrate unusually small thalamic nuclei volumes. Normative modeling enables the identification of these individuals, which is a necessary step toward precision medicine.
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Esquizofrenia , Núcleos Talámicos , Humanos , Esquizofrenia/patología , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/fisiopatología , Adulto , Núcleos Talámicos/patología , Núcleos Talámicos/diagnóstico por imagen , Femenino , Adulto Joven , Adolescente , Masculino , Persona de Mediana Edad , Conectoma , Niño , Imagen por Resonancia Magnética , Preescolar , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Fatigue is frequent in people with multiple sclerosis (pwMS) impacting physical and cognitive functions. Lower aerobic capacity and regional thalamic volume may be involved in the pathophysiology of fatigue in pwMS. OBJECTIVES: To identify associations between thalamic nuclei volumes, aerobic capacity and fatigue and to investigate whether the influence of aerobic capacity on fatigue in pwMS is mediated by thalamic integrity. METHODS: Eighty-three pwMS underwent a clinical evaluation with assessment of fatigue (Modified Fatigue Impact Scale [MFIS]), including physical (pMFIS) and cognitive (cMFIS) components, and peak of oxygen uptake (VO2peak). PwMS and 63 sex- and age-matched healthy controls (HC) underwent a 3 T brain MRI to quantify volume of the whole thalamus and its nuclei. RESULTS: Compared to HC, pwMS showed higher global MFIS, pMFIS and cMFIS scores, and lower VO2peak and thalamic volumes (p < 0.001). In pwMS, higher VO2peak was significantly associated with lower MFIS and pMFIS scores (r value = - 0.326 and - 0.356; pFDR ≤ 0.046) and higher laterodorsal thalamic nucleus (Dor) cluster volume (r value = 0.300; pFDR = 0.047). Moreover, lower Dor thalamic cluster volume was significantly associated with higher MFIS, pMFIS and cMFIS scores (r value range = - 0.305; - 0.293; pFDR ≤ 0.049). The volume of Dor thalamic cluster partially mediated the positive effects of VO2peak on both MFIS and cMFIS, with relative indirect effects of 21% and 32% respectively. No mediation was found for pMFIS. CONCLUSIONS: Higher VO2peak is associated with lower fatigue in pwMS, likely acting on Dor thalamic cluster volume integrity. Such an effect might be different according to the type of fatigue (cognitive or physical).
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Fatiga , Imagen por Resonancia Magnética , Esclerosis Múltiple , Núcleos Talámicos , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Fatiga/etiología , Fatiga/fisiopatología , Fatiga/diagnóstico por imagen , Fatiga/patología , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/fisiopatología , Núcleos Talámicos/diagnóstico por imagen , Núcleos Talámicos/fisiopatología , Núcleos Talámicos/patología , Consumo de Oxígeno/fisiología , Tolerancia al Ejercicio/fisiologíaRESUMEN
BACKGROUND: The thalamus is central to brain functions ranging from primary sensory processing to higher-order cognition. Structural deficits in thalamic association nuclei such as the pulvinar and mediodorsal nuclei have previously been reported in schizophrenia. However, the specificity with regards to clinical presentation, and whether or not bipolar disorder (BD) is associated with similar alterations is unclear. METHODS: We investigated thalamic nuclei volumes in 334 patients with schizophrenia spectrum disorders (SSD) (median age 29 years, 59 % male), 322 patients with BD (30 years, 40 % male), and 826 healthy controls (HC) (34 years, 54 % male). Volumes of 25 thalamic nuclei were extracted from T1-weighted magnetic resonance imaging using an automated Bayesian segmentation method and compared between groups. Furthermore, we explored associations with clinical characteristics across diagnostic groups, including psychotic and mood symptoms and medication use, as well as diagnostic subtype in BD. RESULTS: Significantly smaller volumes were found in the mediodorsal, pulvinar, and lateral and medial geniculate thalamic nuclei in SSD. Similarly, smaller volumes were found in BD in the same four regions, but mediodorsal nucleus volume alterations were limited to its lateral part and pulvinar alterations to its anterior region. Smaller volumes in BD compared to HC were seen only in BD type I, not BD type II. Across diagnoses, having more negative symptoms was associated with smaller pulvinar volumes. CONCLUSIONS: Structural alterations were found in both SSD and BD, mainly in the thalamic association nuclei. Structural deficits in the pulvinar may be of relevance for negative symptoms.
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Esquizofrenia , Humanos , Masculino , Adulto , Femenino , Esquizofrenia/diagnóstico , Teorema de Bayes , Núcleos Talámicos/diagnóstico por imagen , Núcleos Talámicos/patología , Tálamo/patología , Núcleo Talámico Mediodorsal , Imagen por Resonancia Magnética/métodosRESUMEN
Human brain organoids provide unique platforms for modeling several aspects of human brain development and pathology. However, current brain organoid systems mostly lack the resolution to recapitulate the development of finer brain structures with subregional identity, including functionally distinct nuclei in the thalamus. Here, we report a method for converting human embryonic stem cells (hESCs) into ventral thalamic organoids (vThOs) with transcriptionally diverse nuclei identities. Notably, single-cell RNA sequencing revealed previously unachieved thalamic patterning with a thalamic reticular nucleus (TRN) signature, a GABAergic nucleus located in the ventral thalamus. Using vThOs, we explored the functions of TRN-specific, disease-associated genes patched domain containing 1 (PTCHD1) and receptor tyrosine-protein kinase (ERBB4) during human thalamic development. Perturbations in PTCHD1 or ERBB4 impaired neuronal functions in vThOs, albeit not affecting the overall thalamic lineage development. Together, vThOs present an experimental model for understanding nuclei-specific development and pathology in the thalamus of the human brain.
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Núcleos Talámicos , Tálamo , Humanos , Núcleos Talámicos/patología , Núcleos Talámicos/fisiología , Neuronas/fisiología , OrganoidesRESUMEN
INTRODUCTION: This study aimed to investigate the alterations in individual thalamic nuclei volumes in patients with occipital lobe epilepsy (OLE) compared with those of healthy controls, and to analyze the intrinsic thalamic network based on these volumes using graph theory. METHODS: Thirty adult patients with newly diagnosed OLE and 42 healthy controls were retrospectively enrolled (mean age, 33.8 ± 17.0 and 32.2 ± 6.6 years, respectively). The study participants underwent brain magnetic resonance imaging with three-dimensional T1-weighted imaging. The right and left total thalamic and individual thalamic nuclei volumes were obtained using the FreeSurfer program. Then, the intrinsic thalamic network was calculated based on the individual thalamic nuclei volumes and graph theory using a BRAPH program. RESULTS: There were no differences in the right and left whole-thalamic volumes between the two groups (0.445% vs. 0.469%, p = .142 and 0.481% vs. 0.490%, p = .575, respectively). However, significant differences were observed in the volumes of several thalamic nuclei between the two groups. The right medial geniculate and right suprageniculate nuclei volumes were increased (0.0077% vs. 0.0064%, p = .0003 and 0.0013% vs. 0.0010%, p = .0004, respectively), whereas the right and left parafascicular nuclei volumes were decreased in patients with OLE compared with those in healthy controls (0.0038% vs. 0.0048%, p < .0001 and 0.0037% vs. 0.0045%, p = .0001, respectively). There were no differences in the network measures regarding intrinsic thalamic network between the two groups. CONCLUSION: We successfully demonstrated the alterations in individual thalamic nuclei volumes, especially the increased medial geniculate and suprageniculate, and decreased parafascicular nuclei volumes in patients with OLE compared with those of healthy controls despite no changes in the whole-thalamic volumes. These findings suggest an important role of the thalamus in the epileptic network of OLE.
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Epilepsias Parciales , Tálamo , Adulto , Humanos , Adolescente , Adulto Joven , Persona de Mediana Edad , Estudios Retrospectivos , Tálamo/diagnóstico por imagen , Tálamo/patología , Núcleos Talámicos/diagnóstico por imagen , Núcleos Talámicos/patología , Epilepsias Parciales/patología , Encéfalo , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Thalamic atrophy is prominent in multiple sclerosis; however, it is unclear which thalamic nuclei are most vulnerable, especially early in disease. INTRODUCTION: To investigate which thalamic nuclei differ between patients in early stages of relapsing-remitting multiple sclerosis (RRMS) versus healthy controls and examine the relationship between thalamic nuclei volume and T2 lesion volume. METHODS: We derived 15 thalamic subfields from high-resolution 3T magnetic resonance images in 182 patients with early RRMS (diagnosed ≤5.0 years, median 2.0 years). Independent t-tests assessed differences between patients and 35 controls across thalamic subfield volumes. Pearson correlations assessed the relationships between thalamic volumes and T2 lesion volumes. RESULTS: Patients had lower anterior and posterior nuclei volume than controls, whereas medial and ventral nuclei volumes were preserved. Higher T2 lesion volumes were disproportionately related to lower posterior subfield volumes. CONCLUSIONS: We found specific thalamic subfields were more vulnerable to early disease-related changes. We discuss potential mechanisms of differential thalamic subfield atrophy in early MS, including cortical demyelination, CSF toxicity, leptomeningeal inflammation, and iron deposition.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Atrofia/patología , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patología , Núcleos Talámicos/patología , Imagen por Resonancia Magnética/métodos , Enfermedad Crónica , RecurrenciaRESUMEN
INTRODUCTION: Trauma reexperiencing is dominated by recollection of sensory-perceptual elements of the trauma, pointing to involvement of the sensory thalamus. This study examined posttraumatic stress symptoms in relation to volumes of thalamic nuclei that were grouped based on their predominant functions. We hypothesized that reexperiencing, controlling for other symptom dimensions, would correlate with volumes of thalamic nuclei involved in primary and higher-order sensory processing. METHODS: Seventy-two trauma-exposed adults were interviewed with the Clinician Administered PTSD Scale for DSM-IV and underwent 3T magnetic resonance imaging. Scores were derived for reexperiencing, anxious arousal, dysphoric arousal, emotional numbing, and avoidance symptoms. These were entered as simultaneous predictors in five separate regression analyses, with age, sex, and total thalamus volume as covariates, predicting volumesf of five thalamus nuclear groupings corrected for intracranial volume: Specific sensory, associative-sensory, associative-cognitive, intralaminar, and motor groupings. RESULTS: Reexperiencing symptoms were significantly positively correlated with volumes of the motor thalamic grouping, which included the ventral anterior, ventral lateral, and ventromedial nuclei. Anxious arousal was significantly negatively correlated with volumes of all five thalamic groupings. CONCLUSIONS: Reexperiencing symptoms were correlated with volumes of the motor thalamus, while anxious arousal symptoms were related to all thalamic subregion volumes. Thalamic nuclei involved in motor functions, including oculomotor control and motor planning, may be implicated in posttraumatic reexperiencing symptoms.
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Trastornos por Estrés Postraumático , Adulto , Ansiedad/diagnóstico por imagen , Nivel de Alerta , Humanos , Trastornos por Estrés Postraumático/diagnóstico por imagen , Núcleos Talámicos/patología , Tálamo/diagnóstico por imagen , Tálamo/patologíaRESUMEN
PURPOSE: This study aimed to compare the alterations of thalamic nuclei volumes and the intrinsic thalamic network in patients with cluster headache and healthy controls. METHODS: We retrospectively enrolled 24 patients with episodic cluster headache and 24 healthy controls. We calculated the thalamic nuclei volumes in the patients with cluster headache and healthy controls based on three-dimensional T1-weighted imaging with automated segmentation using the FreeSurfer program. We also investigated the intrinsic thalamic network using structural co-variance analysis based on the thalamic nuclei volumes and graph theory under the BRAPH program. We compared the thalamic nuclei volumes and intrinsic thalamic networks in patients with cluster headaches and healthy controls. RESULTS: The right and left whole thalamic volumes did not differ in the patients with cluster headaches and healthy controls (0.4199 vs. 0.4069%, p = 0.2008; 0.4386 vs. 0.4273%, p = 0.3437; respectively). However, there were significant alterations of right and left medial geniculate nuclei volumes in the patients with cluster headaches and the healthy controls. The right and left medial geniculate nuclei volumes of the patients with cluster headaches were greater than those of the healthy controls (0.0088 vs. 0.0075%, p < 0.0001; 0.0086 vs. 0.0072%, p < 0.0001; respectively). The intrinsic thalamic networks of the groups were not different. CONCLUSION: This study demonstrates significant alterations in the bilateral medial geniculate nuclei volumes in patients with cluster headache compared to healthy controls. These alterations may be related to the pathophysiology of cluster headache. However, there are no changes in the intrinsic thalamic network in patients with cluster headache.
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Cefalalgia Histamínica , Núcleos Talámicos , Estudios de Casos y Controles , Cefalalgia Histamínica/diagnóstico por imagen , Cefalalgia Histamínica/patología , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética/métodos , Tamaño de los Órganos , Estudios Retrospectivos , Núcleos Talámicos/diagnóstico por imagen , Núcleos Talámicos/patologíaRESUMEN
OBJECTIVES: To define both the severity and extent of structural alteration in certain thalamic nuclei by means of MR morphometry and to compare these findings with clinical performance in different phenotypes of multiple sclerosis (MS). METHODS: We comparatively measured the thalamus nuclei volumes of patients with remitting-relapsing (RRMS) and secondary-progressive (SPMS) phenotypes of multiple sclerosis and healthy control subjects (HC). The evaluation of neurological performance was based on the results of Expanded Disability Status Scale and Multiple Sclerosis Severity Scale. Cognitive and mental state was rated according to the results of Mini-Mental State Examination, Frontal Assessment Battery, Montreal Cognitive Assessment and Symbol Digit Modalities Test. Freesurfer 6.0 was used for thalamic nuclei volumes calculation. RESULTS: The median volume decline in thalamic pulvinar nuclei in RRMS group on the left side (anterior nucleus - 186,6â¯mm3, posterior nucleus - 149,4â¯mm3, medial nucleus 852,4â¯mm3) compared to HC (anterior nucleus - 229,2â¯mm3, posterior nucleus - 187,5â¯mm3, medical nucleus - 1081,3â¯mm3). Same group, right side - anterior nucleus - 219,5â¯mm3, posterior nucleus 187,1â¯mm3, medial nucleus - 989,6â¯mm3; HC group - anterior nucleus 261,1â¯mm3, posterior nucleus 240,5â¯mm3, medial nucleus - 1196,7â¯mm3 (pâ¯<â¯0,05). The highest correlation of the written section of SDMT was observed with the left ventral anterior nucleus (râ¯=â¯0,71). CONCLUSION: These findings indicate the credible correlation between clinical progression of neurological and cognitive impairment in MS patients with asymmetry left-sided thalamic nuclei atrophy and may be considered a potential predicting tool of MS progression.
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Disfunción Cognitiva/patología , Esclerosis Múltiple/patología , Núcleos Talámicos/patología , Adulto , Atrofia/diagnóstico por imagen , Atrofia/patología , Disfunción Cognitiva/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Pruebas Neuropsicológicas , Núcleos Talámicos/diagnóstico por imagenRESUMEN
BACKGROUND: Increasing evidence suggests that thalamic nuclei may atrophy in Alzheimer's disease (AD). We hypothesized that there will be significant atrophy of limbic thalamic nuclei associated with declining memory and cognition across the AD continuum. OBJECTIVE: The objective of this work was to characterize volume differences in thalamic nuclei in subjects with early and late mild cognitive impairment (MCI) as well as AD when compared to healthy control (HC) subjects using a novel MRI-based thalamic segmentation technique (THOMAS). METHODS: MPRAGE data from the ADNI database were used in this study (nâ=â540). Healthy control (nâ=â125), early MCI (nâ=â212), late MCI (nâ=â114), and AD subjects (nâ=â89) were selected, and their MRI data were parcellated to determine the volumes of 11 thalamic nuclei for each subject. Volumes across the different clinical subgroups were compared using ANCOVA. RESULTS: There were significant differences in thalamic nuclei volumes between HC, late MCI, and AD subjects. The anteroventral, mediodorsal, pulvinar, medial geniculate, and centromedian nuclei were significantly smaller in subjects with late MCI and AD when compared to HC subjects. Furthermore, the mediodorsal, pulvinar, and medial geniculate nuclei were significantly smaller in early MCI when compared to HC subjects. CONCLUSION: This work highlights nucleus specific atrophy within the thalamus in subjects with early and late MCI and AD. This is consistent with the hypothesis that memory and cognitive changes in AD are mediated by damage to a large-scale integrated neural network that extends beyond the medial temporal lobes.
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Enfermedad de Alzheimer/patología , Disfunción Cognitiva/patología , Síntomas Prodrómicos , Núcleos Talámicos/patología , Anciano , Atrofia/patología , Cognición/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria/fisiologíaRESUMEN
ABSTRACT: Thalamic dementia is an uncommon type of stroke that presents with disorientation, behavioral changes, and impairment of executive functions, with relative preservation of motor functions. It is typically caused by paramedian territory infarctions of the thalamus, most often due to ischemic insult at the tip of the basilar artery. In this report, we present a case of bilateral thalamic infarcts resulting in thalamic dementia with severe behavioral manifestations in a 64-yr-old man with no preexisting neuropsychiatric comorbidities. A trial of amantadine, a dopamine-promoting agent, in the acute rehabilitation unit in an attempt to manage his agitation led to multiple weeks of dramatic behavioral improvement and increased participation in therapies. Dopamine receptors are believed to be present at increased densities in thalamic nuclei with mesolimbic projections, suggesting that they are able to modulate limbic functions such as arousal, emotion, and memory. This case report, aimed both to increase the awareness of this uncommon stroke syndrome and describe the observed effect of amantadine, will ultimately help clinicians properly recognize thalamic dementia, minimize unnecessary investigations, and develop effective neurorehabilitation strategies in these patients.
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Amantadina/uso terapéutico , Infarto Cerebral/complicaciones , Infarto Cerebral/tratamiento farmacológico , Demencia/tratamiento farmacológico , Demencia/etiología , Dopaminérgicos/uso terapéutico , Infarto Cerebral/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Núcleos Talámicos/patología , Resultado del TratamientoRESUMEN
INTRODUCTION: This study aimed to investigate the alterations in thalamic nuclei volumes and the intrinsic thalamic structural network in patients with de novo Parkinson's disease (PD) based on their predominant symptoms. METHODS: We enrolled 65 patients with de novo PD (44 patients with tremor-dominant [TD] subtype and 21 patients with postural instability and gait disturbance [PIGD] subtype) and 20 healthy controls. All subjects underwent three-dimensional T1-weighted magnetic resonance imaging. The thalamic nuclei were segmented using the FreeSurfer program. RESULTS: We obtained volumetric differences in the thalamic nuclei of each subtype of PD in comparison of healthy control. Volumes of the right and left suprageniculate nuclei were significantly increased, whereas that of the left parafascicular nucleus was decreased in patients with the TD subtype. Volumes of the right and left suprageniculate nuclei and right ventromedial nucleus were significantly increased, whereas those of the right and left parafascicular nuclei volumes were decreased in patients with the PIGD subtype. The measures of the intrinsic thalamic global network were not different between patients with TD PD and healthy controls. However, in patients with the PIGD subtype, the global and local efficiencies were significantly increased compared to healthy controls. Moreover, although there were no differences in thalamic volume and intrinsic thalamic global network between patients with the TD and PIGD variants, we identified significant differences in the intrinsic thalamic local network between the two groups. CONCLUSIONS: Alterations in thalamic nuclei volumes and the intrinsic thalamic network in patients with PD differed based on their predominant symptoms. These findings might be related to the underlying pathogenesis and suggest that PD is a heterogeneous syndrome.
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Red Nerviosa/patología , Red Nerviosa/fisiopatología , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Núcleos Talámicos/patología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Enfermedad de Parkinson/clasificación , Enfermedad de Parkinson/diagnóstico por imagen , Núcleos Talámicos/diagnóstico por imagenRESUMEN
OBJECTIVE: Thalamus models of psychosis implicate association nuclei in the pathogenesis of psychosis and mechanisms of cognitive impairment. Studies to date have provided conflicting findings for structural deficits specific to these nuclei. The authors sought to characterize thalamic structural abnormalities in psychosis and a neurodevelopmental cohort, and to determine whether nuclear volumes were associated with cognitive function. METHODS: Thalamic nuclei volumes were tested in a cross-sectional sample of 472 adults (293 with psychosis) and the Philadelphia Neurodevelopmental Cohort (PNC), consisting of 1,393 youths (398 with psychosis spectrum symptoms and 609 with other psychopathologies), using a recently developed, validated method for segmenting thalamic nuclei and complementary voxel-based morphometry. Cognitive function was measured with the Screen for Cognitive Impairment in Psychiatry in the psychosis cohort and the Penn Computerized Neurocognitive Battery in the PNC. RESULTS: The psychosis group had smaller pulvinar, mediodorsal, and, to a lesser extent, ventrolateral nuclei volumes compared with the healthy control group. Youths with psychosis spectrum symptoms also had smaller pulvinar volumes, compared with both typically developing youths and youths with other psychopathologies. Pulvinar volumes were positively correlated with general cognitive function. CONCLUSIONS: The study findings demonstrate that smaller thalamic association nuclei represent a neurodevelopmental abnormality associated with psychosis, risk for psychosis in youths, and cognitive impairment. Identifying specific thalamic nuclei abnormalities in psychosis has implications for early detection of psychosis risk and treatment of cognitive impairment in psychosis.
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Trastornos Psicóticos/patología , Núcleos Talámicos/patología , Adulto , Atrofia/patología , Estudios de Casos y Controles , Cognición , Estudios Transversales , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
PURPOSE: To develop a fast and accurate convolutional neural network based method for segmentation of thalamic nuclei. METHODS: A cascaded multi-planar scheme with a modified residual U-Net architecture was used to segment thalamic nuclei on conventional and white-matter-nulled (WMn) magnetization prepared rapid gradient echo (MPRAGE) data. A single network was optimized to work with images from healthy controls and patients with multiple sclerosis (MS) and essential tremor (ET), acquired at both 3 T and 7 T field strengths. WMn-MPRAGE images were manually delineated by a trained neuroradiologist using the Morel histological atlas as a guide to generate reference ground truth labels. Dice similarity coefficient and volume similarity index (VSI) were used to evaluate performance. Clinical utility was demonstrated by applying this method to study the effect of MS on thalamic nuclei atrophy. RESULTS: Segmentation of each thalamus into twelve nuclei was achieved in under a minute. For 7 T WMn-MPRAGE, the proposed method outperforms current state-of-the-art on patients with ET with statistically significant improvements in Dice for five nuclei (increase in the range of 0.05-0.18) and VSI for four nuclei (increase in the range of 0.05-0.19), while performing comparably for healthy and MS subjects. Dice and VSI achieved using 7 T WMn-MPRAGE data are comparable to those using 3 T WMn-MPRAGE data. For conventional MPRAGE, the proposed method shows a statistically significant Dice improvement in the range of 0.14-0.63 over FreeSurfer for all nuclei and disease types. Effect of noise on network performance shows robustness to images with SNR as low as half the baseline SNR. Atrophy of four thalamic nuclei and whole thalamus was observed for MS patients compared to healthy control subjects, after controlling for the effect of parallel imaging, intracranial volume, gender, and age (p < 0.004). CONCLUSION: The proposed segmentation method is fast, accurate, performs well across disease types and field strengths, and shows great potential for improving our understanding of thalamic nuclei involvement in neurological diseases.
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Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética , Redes Neurales de la Computación , Núcleos Talámicos/diagnóstico por imagen , Automatización , Estudios de Casos y Controles , Temblor Esencial/diagnóstico por imagen , Temblor Esencial/patología , Femenino , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Núcleos Talámicos/patología , Adulto JovenRESUMEN
BACKGROUND: Several studies in patients with schizophrenia have demonstrated an abnormal thalamic volume and thalamocortical connectivity. Specifically, hyperconnectivity with somatosensory areas has been related to the presence of auditory hallucinations (AHs). The 22q11.2 deletion syndrome is a neurogenetic disorder conferring proneness to develop schizophrenia, and deletion carriers (22qdel carriers) experience hallucinations to a greater extent than the general population. METHODS: We acquired 442 consecutive magnetic resonance imaging scans from 120 22qdel carriers and 110 control subjects every 3 years (age range: 8-35 years). The volume of thalamic nuclei was obtained with FreeSurfer and was compared between 22qdel carriers and control subjects and between 22qdel carriers with and without AHs. In a subgroup of 76 22qdel carriers, we evaluated the functional connectivity between thalamic nuclei affected in patients experiencing AHs and cortical regions. RESULTS: As compared with control subjects, 22qdel carriers had lower and higher volumes of nuclei involved in sensory processing and cognitive functions, respectively. 22qdel carriers with AHs had a smaller volume of the medial geniculate nucleus, with deviant trajectories showing a steeper volume decrease from childhood with respect to those without AHs. Moreover, we showed an aberrant development of nuclei intercalated between the prefrontal cortex and hippocampus (the anteroventral and medioventral reuniens nuclei) and hyperconnectivity of the medial geniculate nucleus and anteroventral nucleus with the auditory cortex and Wernicke's area. CONCLUSIONS: The increased connectivity of the medial geniculate nucleus and anteroventral nucleus to the auditory cortex might be interpreted as a lack of maturation of thalamocortical connectivity. Overall, our findings point toward an aberrant development of thalamic nuclei and an immature pattern of connectivity with temporal regions in relation to AHs.
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Síndrome de DiGeorge , Alucinaciones , Núcleos Talámicos , Adolescente , Adulto , Niño , Cuerpos Geniculados , Humanos , Núcleos Talámicos/patología , Núcleos Talámicos/fisiopatología , Tálamo/diagnóstico por imagen , Adulto JovenRESUMEN
The thalamus is a key cerebral hub relaying a multitude of corticoefferent and corticoafferent connections and mediating distinct extrapyramidal, sensory, cognitive and behavioural functions. While the thalamus consists of dozens of anatomically well-defined nuclei with distinctive physiological roles, existing imaging studies in motor neuron diseases typically evaluate the thalamus as a single structure. Based on the unique cortical signatures observed in ALS and PLS, we hypothesised that similarly focal thalamic involvement may be observed if the nuclei are individually evaluated. A prospective imaging study was undertaken with 100 patients with ALS, 33 patients with PLS and 117 healthy controls to characterise the integrity of thalamic nuclei. ALS patients were further stratified for the presence of GGGGCC hexanucleotide repeat expansions in C9orf72. The thalamus was segmented into individual nuclei to examine their volumetric profile. Additionally, thalamic shape deformations were evaluated by vertex analyses and focal density alterations were examined by region-of-interest morphometry. Our data indicate that C9orf72 negative ALS patients and PLS patients exhibit ventral lateral and ventral anterior involvement, consistent with the 'motor' thalamus. Degeneration of the sensory nuclei was also detected in C9orf72 negative ALS and PLS. Both ALS groups and the PLS cohort showed focal changes in the mediodorsal-paratenial-reuniens nuclei, which mediate memory and executive functions. PLS patients exhibited distinctive thalamic changes with marked pulvinar and lateral geniculate atrophy compared to both controls and C9orf72 negative ALS. The considerable ventral lateral and ventral anterior pathology detected in both ALS and PLS support the emerging literature of extrapyramidal dysfunction in MND. The involvement of sensory nuclei is consistent with sporadic reports of sensory impairment in MND. The unique thalamic signature of PLS is in line with the distinctive clinical features of the phenotype. Our data confirm phenotype-specific patterns of thalamus involvement in motor neuron diseases with the preferential involvement of nuclei mediating motor and cognitive functions. Given the selective involvement of thalamic nuclei in ALS and PLS, future biomarker and natural history studies in MND should evaluate individual thalamic regions instead overall thalamic changes.
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Esclerosis Amiotrófica Lateral/patología , Proteína C9orf72/genética , Enfermedad de la Neurona Motora/patología , Mutación/genética , Núcleos Talámicos/patología , Anciano , Esclerosis Amiotrófica Lateral/fisiopatología , Atrofia/patología , Encéfalo/patología , Encéfalo/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Neurona Motora/fisiopatología , Neuronas Motoras/patología , Neuronas Motoras/fisiología , Núcleos Talámicos/fisiopatologíaRESUMEN
OBJECTIVES: Down syndrome (DS) is a genetic condition characterized by cognitive disability starting from infancy. Children with DS exhibit deficits in several cognitive domains, including executive function, i.e., a set of cognitive processes that heavily depend on higher-order thalamic nuclei. The goal of this study was to establish whether executive function-related thalamic nuclei of fetuses with DS exhibit neuroanatomical alterations that may contribute to the defects in higher-order control processes seen in children with DS. PATIENTS AND METHODS: In brain sections from fetuses with DS and control fetuses (gestational week 17-22), we evaluated the cellularity in the mediodorsal nucleus (MD), the centromedian nucleus (CM), and the parafascicular nucleus (PF) of the thalamus and the density of proliferating cells in the third ventricle. RESULTS: We found that all three nuclei had a notably reduced cell density. This defect was associated with a reduced density of proliferating cells in the third ventricle, suggesting that the reduced cellularity in the MD, CM, and PF of fetuses with DS was due to neurogenesis impairment. The separate evaluation of projection neurons and interneurons in the MD, CM, and PF showed that in fetuses with DS the density of projection neurons was reduced, with no changes in interneuron density. CONCLUSION: This study provides novel evidence for DS-linked cellularity alterations in the MD, CM, and PF and suggests that altered signal processing in these nuclei may be involved in the impairment in higher-order control processes observed in individuals with DS starting from infancy.